RESUMO
The purpose of the study was to explore the potential of direct exfoliated colonocyte collection from human rectal mucosa for colorectal cancer screening. A special device was designed for standardized collection of exfoliated cells from the surface of human rectal mucosa. Material was collected from 120 outpatients selected for colonoscopy and 36 patients with confirmed diagnosis of colorectal cancer or large polyps. Determination of total DNA amounts in the collected samples (DNA scores) by PicoGreen assay and real-time PCR was employed alongside cytological assessment. Well preserved cells with cytological patterns characteristic for different colorectal conditions (cancer, inflammatory bowel disease) were detected in the collected material. In the outpatient group DNA scores were higher in patients with cancer and inflammatory bowel disease compared to those with no abnormalities detected, diverticular disease and small polyps (P<0.001 for PicoGreen assay; P=0.002 for real-time PCR). The sensitivity and specificity of the quantitative DNA test (PicoGreen assay; cut-off point 3.0 microg/ml) for detecting serious colorectal conditions were 1.00 and 0.74, respectively. In the group with confirmed tumours, the PicoGreen assay performed better for distal colorectal cancer (sensitivity 0.83; specificity 0.76) compared with proximal colon malignancies (sensitivity 0.57; specificity 0.76). It can be concluded that the proposed technique of direct collection of exfoliated cells from the surface of human rectal mucosa provides abundant cellular material suitable for diagnostic and research applications. Further refinement of the quantitative DNA test may lead to a new approach for colorectal cancer early detection and screening.
Assuntos
Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , DNA de Neoplasias/análise , Mucosa Intestinal/patologia , Reto/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colo/patologia , Colo Sigmoide/patologia , Neoplasias Colorretais/patologia , Primers do DNA , Feminino , Humanos , Pólipos Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Curva ROC , Sensibilidade e EspecificidadeRESUMO
It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-ß.